Cholesterol Depletion by MβCD Enhances Cell Membrane Tension and Its Variations-Reducing Integrity.


Journal

Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626

Informations de publication

Date de publication:
23 04 2019
Historique:
received: 09 07 2018
revised: 22 01 2019
accepted: 14 03 2019
pubmed: 14 4 2019
medline: 11 6 2020
entrez: 14 4 2019
Statut: ppublish

Résumé

Cholesterol depletion by methyl-β-cyclodextrin (MβCD) remodels the plasma membrane's mechanics in cells and its interactions with the underlying cytoskeleton, whereas in red blood cells, it is also known to cause lysis. Currently it's unclear if MβCD alters membrane tension or only enhances membrane-cytoskeleton interactions-and how this relates to cell lysis. We map membrane height fluctuations in single cells and observe that MβCD reduces temporal fluctuations robustly but flattens spatial membrane undulations only slightly. Utilizing models explicitly incorporating membrane confinement besides other viscoelastic factors, we estimate membrane mechanical parameters from the fluctuations' frequency spectrum. This helps us conclude that MβCD enhances membrane tension and does so even on ATP-depleted cell membranes where this occurs despite reduction in confinement. Additionally, on cholesterol depletion, cell membranes display higher intracellular heterogeneity in the amplitude of spatial undulations and membrane tension. MβCD also has a strong impact on the cell membrane's tenacity to mechanical stress, making cells strongly prone to rupture on hypo-osmotic shock with larger rupture diameters-an effect not hindered by actomyosin perturbations. Our study thus demonstrates that cholesterol depletion increases membrane tension and its variability, making cells prone to rupture independent of the cytoskeletal state of the cell.

Identifiants

pubmed: 30979551
pii: S0006-3495(19)30203-6
doi: 10.1016/j.bpj.2019.03.016
pmc: PMC6486507
pii:
doi:

Substances chimiques

beta-Cyclodextrins 0
methyl-beta-cyclodextrin 0
Adenosine Triphosphate 8L70Q75FXE
Cholesterol 97C5T2UQ7J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1456-1468

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/I/13/1/500885
Pays : India

Informations de copyright

Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.

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Auteurs

Arikta Biswas (A)

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.

Purba Kashyap (P)

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.

Sanchari Datta (S)

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.

Titas Sengupta (T)

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India.

Bidisha Sinha (B)

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, West Bengal, India. Electronic address: bidisha.sinha@iiserkol.ac.in.

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Classifications MeSH